ABSTRACT
The spinal origin of cholestatic itch in experimental obstructive jaundice mouse model remains poorly understood.In this study,the jaundice model was established by bile duct ligation (BDL) in mice,and differential gene expression patterns were analyzed in the lower thoracic spinal cord involved in cholestatic pruritus after BDL operation using high-throughput RNA sequencing.At 21st day after BDL,the expression levels of ENSRNOG00000060523,ENSRNOG00000058405 and ENSRNOG00000055193 mRNA were significantly up-regulated,and those of ENSRNOG00000042197,ENSRNOG00000008478,ENSRNOG00000019607,ENSRNOG00000020647,ENSRNOG00000046289,Gemin8,Serpina3n and Trim63 mRNA were significantly down-regulated in BDL group.The RNAseq data of selected mRNAs were validated by RT-qPCR.The expression levels of ENSRNOG00000042197,ENSRNOG00000008478,ENSRNOG00000019607,ENSRNOG00000020647,ENSRNOG00000046289 and Serpina3n mRNA were significantly down-regulated in BDL group.This study suggested that cholestatic pruritus in experimental obstructive jaundice mouse model is related with in the changes of gene expression profiles in spinal cord.
ABSTRACT
The spinal origin of cholestatic itch in experimental obstructive jaundice mouse model remains poorly understood.In this study,the jaundice model was established by bile duct ligation (BDL) in mice,and differential gene expression patterns were analyzed in the lower thoracic spinal cord involved in cholestatic pruritus after BDL operation using high-throughput RNA sequencing.At 21st day after BDL,the expression levels of ENSRNOG00000060523,ENSRNOG00000058405 and ENSRNOG00000055193 mRNA were significantly up-regulated,and those of ENSRNOG00000042197,ENSRNOG00000008478,ENSRNOG00000019607,ENSRNOG00000020647,ENSRNOG00000046289,Gemin8,Serpina3n and Trim63 mRNA were significantly down-regulated in BDL group.The RNAseq data of selected mRNAs were validated by RT-qPCR.The expression levels of ENSRNOG00000042197,ENSRNOG00000008478,ENSRNOG00000019607,ENSRNOG00000020647,ENSRNOG00000046289 and Serpina3n mRNA were significantly down-regulated in BDL group.This study suggested that cholestatic pruritus in experimental obstructive jaundice mouse model is related with in the changes of gene expression profiles in spinal cord.
ABSTRACT
Substantial evidence has suggested that deep brain stimulation of the cuneiform nucleus has become a remarkable treatment option for intractable pain, but the possible mechanism is poorly understood. Using a melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) reporter knockin mouse, we showed that a large number of MC4R-GFP-positive neurons were expressed in the cuneiform nucleus. Immunofluorescence revealed that approximately 40%-50% of MC4R-GFP-positive neurons expressed mu opioid receptors, indicating that they were opioidergic signaling. Our findings support the hypothesis that MC4R expression in the cuneiform nucleus is involved in the modulation of opioidergic signaling.
Subject(s)
Animals , Mice , Gene Expression Regulation , Gene Knock-In Techniques , Genes, Reporter , Green Fluorescent Proteins , Genetics , Metabolism , Mice, Transgenic , Microtomy , Midbrain Reticular Formation , Cell Biology , Metabolism , Neurons , Cell Biology , Metabolism , Receptor, Melanocortin, Type 4 , Genetics , Metabolism , Receptors, Opioid, mu , Genetics , Metabolism , Recombinant Fusion Proteins , Genetics , Metabolism , Signal TransductionABSTRACT
A collection of neurons in the upper lumbar spinal cord (lumbar segments 3 and 4) of male rats project to the lower lumbar spinal cord (lumbar segments 5 and 6) and release a gastrin-releasing peptide (GRP) to the somatic and autonomic regions, which are known to regulate male sexual reflexes. The GRP plays some special functions when bound to the specific GRP receptor (GRPR). The spinal GRP system is regulated by androgens. Accumulating evidence shows that GRP plays an important role in rat penile erection and ejaculation, and pharmacological stimulation of GRPRs with a specific agonist can restore penile reflexes and ejaculation in castrated male rats. Therefore, the GRP system appears to be a potential therapeutic target for the treatment of erectile dysfunction or ejaculatory dysfunction. The present paper briefly reviews the recent studies on the role of the spinal GRP system in regulating the sexual function of males.
Subject(s)
Animals , Male , Rats , Androgens , Metabolism , Ejaculation , Physiology , Gastrin-Releasing Peptide , Metabolism , Physiology , Penile Erection , Physiology , Spinal Cord , MetabolismABSTRACT
The rostral ventromedial medulla (RVM) is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor (MC4R) expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus (NRM) and nucleus gigantocellularis pars α (NGCα)]. Fluorescence immunohistochemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryptophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.
Subject(s)
Animals , Female , Male , Mice , Medulla Oblongata , Cell Biology , Metabolism , Mice, Transgenic , Neural Pathways , Cell Biology , Metabolism , Neurons, Afferent , Cell Biology , Metabolism , Nociception , Physiology , Receptor, Melanocortin, Type 4 , Genetics , Metabolism , Serotonergic Neurons , Metabolism , Tyrosine 3-Monooxygenase , MetabolismABSTRACT
The rostral ventromedial medulla (RVM) is a prominent component of the descending modulatory system involved in the control of spinal nociceptive transmission. In the current study, we investigated melanocortin-4 receptor (MC4R) expression in the RVM, where the neurons involved in modulation of nociception reside. Using a line of mice expressing green fluorescent protein (GFP) under the control of the MC4R promoter, we found a large number of GFP-positive neurons in the RVM [nucleus raphe magnus (NRM) and nucleus gigantocellularis pars α (NGCα)]. Fluorescence immunohistochemistry revealed that approximately 10% of MC4R-GFP-positive neurons coexpressed tyrosine hydroxylase, indicating that they were catecholaminergic, whereas 50%-75% of those coexpressed tryptophan hydroxylase, indicating that they were serotonergic. Our findings support the hypothesis that MC4R signaling in RVM may modulate the activity of serotonergic sympathetic outflow sensitive to nociceptive signals, and that MC4R signaling in RVM may contribute to the descending modulation of nociceptive transmission.